The goal of the proposed studies is to investigate whether peripheral treatment of focal dystonias with botulinum toxin (BTX) injections leads to a reduction or change in functional and structural brain abnormalities observed in these patients. It has been hypothesized that BTX may benefit dystonia patients in part by altering afferent feedback to the brain, and consequently changing brain activity in some way which reduces abnormal motor output. There is only a minimal amount of evidence for such effects, and the studies showing this evidence have raised specific questions requiring further investigation. In the proposed studies we will use brain imaging techniques to evaluate the effects of BTX injections on brain function (fMRI) and structure (diffusion tensor imaging [DTI]) in dystonia. We will do this using a set of experimental design and analysis techniques which we have developed to be sensitive to brain abnormalities in sensorimotor circuitry and in dystonia. We will first establish baseline abnormalities in a population of focal dystonia patients (Aim 1), which can then be re-evaluated in these same patients after treatment (Aim 2). In addition to measuring brain activity during tasks which trigger dystonia, we will measure brain activity during motor tasks which do not trigger dystonia and during the period after task completion to evaluate the effects of treatment on the brain sensorimotor system independent of task performance strategy.
In Aim 3 we will show preliminary evidence that some changes after treatment may be cumulative and potentially reflect brain plasticity. We will make measurements at two different time-points after treatment to show that functional and structural normalization increases across the time period that treatment is effective. Relevance to public health: This research study uses brain imaging technology to show that brain structure and function appear more normal in patients with dystonia after their symptoms are treated with botulinum toxin injections. This is the first step toward our long-term goal of showing that this treatment may help to reduce or prevent progression of brain abnormalities in this disorder. Such a finding would argue the importance of early and effective treatment and provide valuable information needed for developing new, improved treatments for the disorder.
| Waugh, Jeff L; Kuster, John K; Levenstein, Jacob M et al. (2016) Thalamic Volume Is Reduced in Cervical and Laryngeal Dystonias. PLoS One 11:e0155302 |
| Blood, Anne J (2013) Imaging studies in focal dystonias: a systems level approach to studying a systems level disorder. Curr Neuropharmacol 11:3-15 |
| Blood, Anne J; Kuster, John K; Woodman, Sandra C et al. (2012) Evidence for altered basal ganglia-brainstem connections in cervical dystonia. PLoS One 7:e31654 |
| Kim, Byoung Woo; Kennedy, David N; Lehár, Joseph et al. (2010) Recurrent, robust and scalable patterns underlie human approach and avoidance. PLoS One 5:e10613 |
| Blood, Anne J; Iosifescu, Dan V; Makris, Nikos et al. (2010) Microstructural abnormalities in subcortical reward circuitry of subjects with major depressive disorder. PLoS One 5:e13945 |
| Blood, Anne J (2008) New hypotheses about postural control support the notion that all dystonias are manifestations of excessive brain postural function. Biosci Hypotheses 1:14-25 |
